ABSTRACT This project applies basic affective science methodology to assess socioemotional functioning in patients with frontotemporal dementia (FTD) and Alzheimer's disease (AD). By measuring multiple emotion processes (reactivity, regulation, and recognition), types (positive, negative, self-conscious emotions), and response systems (subjective experience, expressive behavior, peripheral physiology, emotional language), we obtain an unusually comprehensive and fine-grained assessment of socioemotional functioning. Using this approach, we have identified particular aspects of socioemotional functioning that distinguish among FTD-spectrum disorders, AD, and normal aging. This assessment has also been well-suited for establishing links with anatomical data derived from structural neuroimaging and post-mortem neuropathology. In the next project period, we will expand this research to include: (a) psychiatric patients with major depressive disorder (MDD) and bipolar affective disorder (BD), which also produce changes in socioemotional functioning and can be difficult to distinguish from dementia in late life; (b) additional measures of social/interpersonal functioning in the realms of emotional reactivity (pride, an emotion that arises from complex social comparisons), regulation (social down-regulation of response to stress associated with presence of caregiver), and recognition (continuous ratings of one's own emotions, recognizing comfortable interpersonal distance); (c) new measures of autonomic nervous system functioning (stomach activity) and visceral awareness (gastric filling); (d) longitudinal assessments of patients' real-world socioemotional functioning; and (e) additional imaging measures (PET assays of tau and amyloid accumulation and circuit-focused assessment of functional connectivity. We will pursue three specific aims: Aim 1. Social/Interpersonal functioning. We will utilize our expanded assessment of social/interpersonal functioning to characterize social/interpersonal functioning in FTD-spectrum disorders, AD, MDD, and BD; Aim 2. Difficult diagnoses. We will identify optimal groups of predictors from our laboratory-assessment of socioemotional functioning for distinguishing among patients with FTD, AD, MDD, and BD. Aim 3. Brain-behavior relationships. We will delineate brain circuitry associated with deficits in specific aspects of emotional reactivity, regulation, and recognition. Innovations of this project include: (a) applying basic affective science methodology to characterize social and emotional functioning in patients with dementia and mood disorders; (b) using classification analysis techniques with strong criterion measures (state-of-the-art clinical diagnoses, and, when possible, autopsy-confirmed diagnoses) to identify optimal groups of predictors for increasing diagnostic accuracy; and (c) studying brain-behavior relationships using fine-grained measures of emotional reactivity, regulation, and recognition linked with anatomical data derived from MRI and PET imaging, functional connectivity analyses, and autopsy-based neuropathology focused on selectively vulnerable brain regions.